11-16789264-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001329630.2(PLEKHA7):c.3189A>C(p.Ser1063=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,613,628 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (3 hom., cov: 33)
  • Exomes 𝑓: 0.000099 (0 hom.)
• Consequence: PLEKHA7 NM_001329630.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.222

Genes affected

PLEKHA7 (HGNC:27049): (pleckstrin homology domain containing A7) Enables delta-catenin binding activity. Involved in epithelial cell-cell adhesion; pore complex assembly; and zonula adherens maintenance. Located in several cellular components, including centrosome; nucleoplasm; and zonula adherens. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013082981).
• BP6: Variant 11-16789264-T-G is Benign according to our data. Variant chr11-16789264-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3037586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.222 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA7	NM_001329630.2	c.3189A>C	p.Ser1063=	synonymous_variant	23/27	ENST00000531066.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA7	ENST00000531066.6	c.3189A>C	p.Ser1063=	synonymous_variant	23/27	5	NM_001329630.2	A1

Frequencies

GnomAD3 genomes AF: 0.000946 AC: 144 AN: 152166 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.000253 AC: 63 AN: 248628 Hom.: 0 AF XY: 0.000163 AC XY: 22 AN XY: 134642

Gnomad AFR exome AF: 0.00351

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.0000985 AC: 144 AN: 1461344 Hom.: 0 Cov.: 31 AF XY: 0.0000743 AC XY: 54 AN XY: 727004

Gnomad4 AFR exome AF: 0.00332

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.000248

GnomAD4 genome AF: 0.000946 AC: 144 AN: 152284 Hom.: 3 Cov.: 33 AF XY: 0.000913 AC XY: 68 AN XY: 74464

Gnomad4 AFR AF: 0.00296

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000585 Hom.: 0

Bravo AF: 0.00106

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000280 AC: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PLEKHA7-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	6.9
Dann	Benign	0.91
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.61	D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	D;D;D;N
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.54
Vest4		0.27
MVP		0.25
ClinPred		0.070	T
GERP RS		-1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149883568; hg19: chr11-16810811;